About

Dr. Richard Kirian is an Associate Professor in the Department of Physics at Arizona State University, with additional affiliations including the Biodesign Beus CXFEL Lab, the Center for Biological Physics, and the Biodesign Center for Applied Structural Discovery. His primary research focuses on the field of x-ray free-electron laser science, where he develops experimental measurement and diffraction analysis techniques for static and time-resolved studies of biological macromolecules. His work involves advancing three main techniques: femtosecond serial crystallography, time-resolved solution scattering, and single-molecule imaging. Dr. Kirian also develops particle injection systems for biomolecules and innovates new lensless diffractive imaging techniques. He earned his Ph.D. in physics from Arizona State University in 2011 and completed postdoctoral work at the Center for Free-Electron Lasers in Hamburg from 2011 to 2014. His research contributions include imaging single cells with X-ray lasers, developing aerosol injectors for single-particle diffractive imaging, and direct phasing of finite crystals illuminated with free-electron lasers. His expertise areas include the physics of biological systems and soft matter physics.

Research topics

• Computer Science
• Optics
• Chemistry
• Materials science
• Physics
• Nanotechnology
• Crystallography
• Biochemistry
• Biology
• Chromatography
• Genetics
• Nuclear physics
• Mechanics
• Telecommunications
• Biophysics

Selected publications

• Signal extraction in SWAXS data for the compact X-ray light sources: a machine learning approach

  Scientific Reports · 2026-04-07

  articleOpen access

  The development of X-ray free electron lasers has driven significant progress in X-ray science. Given the broad range of their applications, implementing a new generation of this technology at the laboratory scale has been under consideration for several years. This initiative is now under commissioning and construction at Arizona State University, known as the Compact X-ray Light Source (CXLS) and the Compact X-ray Free Electron Laser (CXFEL). Alongside experimental advances in this direction, whether in large or compact X-ray free electron lasers, there is also a growing need for new algorithmic and analytical methods to process the data obtained from such facilities. This work introduces a novel approach for analyzing Small- and Wide-Angle X-ray Scattering (SWAXS) profiles using a data-driven machine learning algorithm. The method is proposed for application to SWAXS datasets collected at both compact and large-scale X-ray facilities. To evaluate the performance of this approach, we analyzed simulated time-resolved SWAXS data from a protein, generated based on the current CXLS experimental parameters, and compared the results with those from the standard singular value decomposition (SVD) technique. Despite the low photon counts in the data, the results demonstrate that our method achieves higher accuracy in extracting structural dynamics information compared to SVD.

  PublisherOA PDFDOI

• Minimized sample consumption for time-resolved serial crystallography applied to the redox cycle of human NQO1

  Communications Chemistry · 2026-01-29

  articleOpen access

  Sample consumption for serial femtosecond crystallography with X-ray free electron lasers remains a major limitation preventing broader use in macromolecular crystallography. This drawback is exacerbated in time-resolved (TR) experiments, where the amount of sample required per reaction time point is multiplied by the number of time points investigated. To reduce this limitation, we demonstrate a segmented droplet generation strategy coupled to a mix-and-inject approach for TR studies at the European XFEL. The injector produces synchronized droplet trains that enable stable and reproducible injection of protein crystal slurries at significantly reduced flow rates. Using the human flavoenzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) as a test system, we collected diffraction data after mixing with NADH at 0.3 s and 1.2 s delays. The segmented injection approach achieved up to 97% reduction in sample consumption compared with continuous-flow injection while maintaining data quality suitable for TR crystallography. Reproducible electron density features consistent with low-occupancy NADH binding illustrate both the feasibility and the current limits of studying dynamic redox enzymes using this approach. This work establishes segmented droplet generation as a sample-efficient and XFEL-compatible method for future time-resolved serial crystallography experiments.

  PublisherOA PDFDOI

• BPS2026 – Time-resolved X-ray scattering explores ultrafast structural changes of visual rhodopsin

  Biophysical Journal · 2026-02-01

  article
  PublisherDOI

• BPS2025 - Ultrafast membrane protein dynamics with femtosecond time-resolved X-ray solution scattering

  Biophysical Journal · 2025-02-01

  article
  PublisherDOI

• BPS2025 - Liquid nano-sheet sample delivery for femtosecond solution X-ray scattering

  Biophysical Journal · 2025-02-01

  articleSenior author
  PublisherDOI

• Data Analysis tools for the Compact X-ray Light Source and Compact X-ray Free Electron Laser facilities at Arizona State University

  Structural Dynamics · 2025-09-01

  articleOpen accessSenior author

  The Compact X-ray Light Source (Figure 1) and Compact X-ray Free Electron Laser [1], [2] that are currently undergoing commissioning and construction, respectively, at Arizona State University will be the first of their kind with applications in structural biology, medical imaging, atomic, molecular and optical physics as well as studying condensed matter and quantum materials. The unique characteristics of the ultrashort X-ray pulses produced by both sources at kilohertz repetition rates necessitate novel and new data analysis algorithms and tools as well as supportive cyber infrastructure at ASU. Here we will report on the current state of the data analysis support and tools currently under development at CXLS/CXFEL for studying biological macromolecules at these sources for both online (real- time) and offline analysis. These include an AI/ML-based crystal hitfinder, integration of an AI/ML-based image sorter [3], Small Angle X-ray Scattering analysis tools, calibration pipelines etc.

  PublisherOA PDFDOI

• Synchronized droplet nozzle for in-vacuum X-ray scattering experiments

  Lab on a Chip · 2025-01-01

  articleOpen accessSenior author

  piezoelectric transduction. A co-flowing helium sheath gas allows the droplets to eject into vacuum, which minimizes X-ray gas background scatter. Alternatively, the system can operate at atmospheric pressure without the need for humidity control. A control system enhances the synchronization such that 60% of droplet positions fall within 25% of the droplet diameter. Numerical simulations are presented that match well with experimental data and reveal recirculation patterns in the meniscus, along with a detailed view of the dynamics associated with onset of triggered synchronization. The system is designed such that it can be implemented at conventional end-stations at XFEL and synchrotron facilities with minimal modification.

  PublisherOA PDFDOI

• Temporal ghost imaging for pump–probe X-ray solution scattering

  Acta Crystallographica Section A Foundations and Advances · 2025-07-07

  articleOpen accessSenior author

  Time-resolved small- and wide-angle X-ray scattering is a valuable tool for investigating biomolecular dynamics on a wide variety of timescales, without cryo-freezing or crystallization. However, some systems, such as the initial excitation of photo-active proteins, evolve dynamically on timescales that may be faster than the duration of the pump and probe beams. Data from a single pump-probe pulse pair therefore contain information from a mixture of time points. In this work, a simple algorithm is developed to recover the dynamics of solution scattering profiles. It leverages information about the pump and probe pulse beams' temporal profiles by using the same mathematical framework as ghost imaging [Pittman et al. (1995). Phys. Rev. A 52, R3429-R3432; Bennink et al. (2002). Phys. Rev. Lett. 89, 113601; Gatti et al. (2004). Phys. Rev. Lett. 93, 093602]. Results from several simulated data sets are presented.

  PublisherOA PDFDOI

• Minimized Sample Consumption for Time-Resolved Serial Crystallography Applied to the Redox Cycle of Human NQO1

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-04-29 · 3 citations

  preprintOpen access

  Abstract Sample consumption for serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) remains a major limitation preventing broader use of this powerful technology in macromolecular crystallography. This drawback is exacerbated in the case of time-resolved (TR)-SFX experiments, where the amount of sample required per reaction time point is multiplied by the number of time points investigated. Thus, in order to reduce the limitation of sample consumption, here we demonstrate the implementation of segmented droplet generation in conjunction with a mix-and-inject approach for TR studies on NAD(P)H:quinone oxidoreductase 1 (NQO1). We present the design and application of mix-and-inject segmented droplet injectors for the Single Particles, Clusters, and Biomolecules & Serial Femtosecond Crystallography (SPB/SFX) instrument at the European XFEL (EuXFEL) with a synchronized droplet injection approach that allows liquid phase protein crystal injection. We carried out TR-crystallography experiments with this approach for a 305 ms and a 1190 ms time point in the reaction of NQO1 with its coenzyme NADH. With this successful TR-SFX approach, up to 97% of the sample has been conserved compared to continuous crystal suspension injection with a gas dynamic virtual nozzle. Furthermore, the obtained structural information for the reaction of NQO1 with NADH is an important part of the future elucidation of the reaction mechanism of this crucial therapeutic enzyme.

  PublisherOA PDFDOI

• Resolving non-equilibrium shape variations amongst millions of gold nanoparticles

  arXiv (Cornell University) · 2024-01-01

  preprintOpen access

  Nanoparticles, exhibiting functionally relevant structural heterogeneity, are at the forefront of cutting-edge research. Now, high-throughput single-particle imaging (SPI) with x-ray free-electron lasers (XFELs) creates unprecedented opportunities for recovering the shape distributions of millions of particles that exhibit functionally relevant structural heterogeneity. To realize this potential, three challenges have to be overcome: (1) simultaneous parametrization of structural variability in real and reciprocal spaces; (2) efficiently inferring the latent parameters of each SPI measurement; (3) scaling up comparisons between $10^5$ structural models and $10^6$ XFEL-SPI measurements. Here, we describe how we overcame these three challenges to resolve the non-equilibrium shape distributions within millions of gold nanoparticles imaged at the European XFEL. These shape distributions allowed us to quantify the degree of asymmetry in these particles, discover a relatively stable `shape envelope' amongst nanoparticles, discern finite-size effects related to shape-controlling surfactants, and extrapolate nanoparticles' shapes to their idealized thermodynamic limit. Ultimately, these demonstrations show that XFEL SPI can help transform nanoparticle shape characterization from anecdotally interesting to statistically meaningful.

  PublisherOA PDFDOI

Recent grants

• ABI Innovation: New Algorithms for Biological X-ray Free Electron Laser Data

  NSF · $762k · 2016–2020

• CAREER: Imaging dynamic macromolecules in solution with x-ray lasers

  NSF · $1.1M · 2020–2027

Frequent coauthors

• Henry N. Chapman

  Max Planck Institute for the Structure and Dynamics of Matter

  357 shared

• Anton Barty

  191 shared

• Jochen Küpper

  Center for Free-Electron Laser Science

  129 shared

• Kenneth R. Beyerlein

  Institut National de la Recherche Scientifique

  124 shared

• Salah Awel

  117 shared

• Richard Bean

  European X-Ray Free-Electron Laser

  116 shared

• Oleksandr Yefanov

  114 shared

• Daniel A. Horke

  110 shared

Labs

• Biodesign Beus CXFEL LabPI

  Develops experimental measurement and diffraction analysis techniques for static and time-resolved studies of biological macromolecules.

Education

• Ph.D., Physics

  Arizona State University

  2011

• B.A., Astronomy

  University of California-Berkeley

  2006

• B.A., Physics

  University of California-Berkeley

  2006